The small-molecule inhibitor NT157 has been previously reported to promote IGF1R/IRS pathway inhibition through proteasomal degradation of IRS1/2 and antineoplastic activity in solid tumors.21–26 In the present study, we used this molecule to inhibit IRS2, a key adaptor protein in JAK2 (refs. 17,18,27) and IGF1R28,29 signaling, and characterized the efficacy of NT157 treatment in the context of JAK2V617F-positive MPN. Here, IGF1R is linked to myeloproliferative neoplasm.